COPD Drug Offers Some Benefit in Asthma

Action Points

Long­ acting beta-agonists in combination with inhaled glucocorti­coids have become standard treatment for pa­tients with asthma that is poorly controlled while receiving inhaled glucocorticoids alone. Although this treatment is effective in a majority of pa­tients, some still have poor asthma control.

Note that these two randomized controlled studies suggest that add-­on ther­apy with the long ­acting anticholinergic agent tiotropium, which inhibits smooth­ muscle contraction and mucus secretion, provided sustained bronchodilation and resulted in reduced asthma exacerbations in patients who were symptomatic and had persistent airflow limitation despite the use of LABAs and inhaled glucocorticoids.

A drug widely used in chronic obstructive pulmonary disease (COPD) is also effective in patients with asthma that is poorly controlled despite standard combination therapy, researchers reported.

In two identical randomized placebo-controlled trials, tiotropium (Spiriva) improved bronchodilation -- modestly but significantly -- after 24 weeks of daily use along with standard therapy, according to Huib Kerstjens, MD, of the University Medical Center Groningen in Groningen, the Netherlands, and colleagues.

The drug also delayed the time to first severe exacerbation of the disease, Kerstjens and colleagues reported online in the New England Journal of Medicine and at the European Respiratory Society meeting in Vienna.

Many asthma patients have poorly controlled disease despite taking inhaled glucocorticoids with or without inhaled long-acting beta-agonists, the researchers noted, so additional bronchodilating drugs would be useful.

The long-acting anticholinergic bronchodilator tiotropium has been approved to treat COPD, and there is some evidence of efficacy in asthma. But its effect has not been tested in long-term trials with enough power to allow analysis of important endpoints.

To help fill the gap, Kerstjens and colleagues conducted two studies with the same design – dubbed trial 1 and trial 2 – that randomly assigned patients with poorly controlled asthma to use either tiotropium or a placebo, both delivered using a fine-mist inhaler (Respimat) daily for 48 weeks.

The primary endpoints were change from baseline after 24 weeks in 1-second forced expiratory volume (FEV1), both before and after dosing. A third endpoint was the time to first severe exacerbation, measured at 48 weeks.

All 912 randomized patients were symptomatic, had a post-bronchodilator FEV1 of 80% or less of the predicted value, and had experienced at least one severe exacerbation in the previous year.

The researchers found at 24 weeks, the average change in the post-dose FEV1 from baseline was greater with tiotropium than placebo – a difference from placebo of 86 ml in trial 1 (P=0.01) and 154 ml in trial 2 (P<0.001).

The same was true for pre-dose FEV1 -- a difference from placebo of 88 ml in trial 1 (P=0.01) and 111 ml in trial 2 (P<0.001).

Adding tiotropium to patients' standard therapy increased the time to the first severe exacerbation by nearly 60 days – 282 days compared with 226 -- with an overall 21% reduction in the risk of a severe exacerbation (hazard ratio 0.79, P=0.03.)

But some limitations of the study make it only a "valuable but intermediate step toward safe application of long-acting anticholinergic agents in patients with asthma," argued Elisabeth Bel, MD, PhD, of the Academic Medical Center in Amsterdam.

In an accompanying editorial, Bel noted that the researchers selected patients with persistent airflow limitations whose condition was similar to that of nonsmokers with COPD.

"It is not inconceivable that the beneficial effects of tiotropium are restricted to such nonsmoking, COPD-look-alike patients with asthma," she commented.

The researchers also excluded patients with previous heart disease, she noted. But tiotropium, delivered deep into the lung with the Respimat device, might be risky for people with a history of cardiovascular events, she wrote.

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